Cataract extraction is among the most commonly performed operations in the United States and the world. A cataractous lens is located within a capsular sac or lens capsule in the posterior chamber of the eye. In order to gain access to the cataractous lens, an incision typically is made at the limbus of the eye for the purpose of introducing a surgical instrument into the anterior chamber of the eye. In the case of extracapsular cataract extraction, a capsularhexis procedure is performed in which a portion of the anterior membrane of the lens capsule adjacent to the iris is removed using a surgical cutting instrument in order to provide direct access to the cataractous lens from the anterior chamber. The diseased lens is then removed through various known methods, including phacoemulsification. Phacoemulsification is a procedure entailing the application of ultrasonic energy to the diseased lens in order to break the cataractous lens into small pieces that can be aspirated from the lens capsule. With the exception of the portion of the anterior membrane of the lens capsule removed during the capsularhexis procedure, the lens capsule remains substantially intact throughout an extracapsular cataract extraction. Following removal of the cataractous lens, an artificial intraocular lens (IOL) implant is typically implanted within the lens capsule in order to mimic the refractive function of the lens.
Although cataractous lens removal with IOL implant replacement provides significant benefits to most cataract patients, it is estimated that up to fifty percent (50%) of all patients who have IOL implants placed within the lens capsule will develop posterior capsular opacification (PCO) or secondary cataracts within five years after surgery. PCO is caused by the deposit of cells and fibers on the IOL implant and on the posterior capsular membrane, thereby obstructing light passing through the IOL implant and obscuring the patient's vision. These cell deposits originate from two sources: (1) the proliferation of residual lens epithelial cells on the interior surface of the lens capsule after surgery; and (2) the accumulation of inflammatory cells and protein deposits on the intraocular lens implant. Of these two sources, the major cause of PCO by far is the proliferation and migration of the residual lens epithelial cells on the capsular membrane.
Ophthalmic surgeons, aware of the problems associated with residual lens epithelial cells, typically take considerable care in trying to remove all residual lens epithelial cells prior to the implantation of an artificial IOL implant. However, despite these efforts, a significant number of lens epithelial cells usually are left on the interior surface of the lens capsule due to the fact that these cells are difficult to identify and are often difficult to reach due to their position on the inside surface of the lens capsule.
The most common treatment for PCO entails the application of laser energy to the posterior membrane of the lens capsule for the purpose of destroying the lens epithelial cells propagating thereon. However, the laser energy applied to the posterior membrane of the lens capsule is ordinarily directed through the IOL implant possibly resulting in damage to the optical and/or structural characteristics of the IOL implant. The application of laser energy to the posterior membrane of the lens capsule also typically results in the destruction of a portion of the lens capsule as well as the residual lens epithelial cells propagating thereon. The destruction of a portion of the lens capsule creates a risk of exposure to the vitreous, possibly resulting in serious or irreparable damage to the eye. In addition, the destruction of a portion of the lens capsule creates a risk of shrinkage of the lens capsule, which may result in a compromise in the optical characteristics of the IOL implant. In certain cases, the destroyed posterior capsular tissue may also regenerate, e.g., as a result of a fibrin clot. Accordingly, it is preferable to prevent the occurrence of PCO rather than attempting to treat it at a later date through the application of laser energy.
Various procedures for the prevention of PCO have been suggested in recent years. Many such procedures have included the application of chemicals to the interior surface of the lens capsule in order to destroy residual lens epithelial cells. However, none of these procedures has proven to be particularly successful in the prevention of PCO due to the fact that it is extremely difficult to destroy residual lens epithelial cells without simultaneously destroying other cells within the eye, including the possible destruction of the corneal endothelium. Selective destruction of residual lens epithelial cells thus appears to be the key to the prevention of PCO.
Antimetabolites such as 5FU and daunomycin have been injected into the lens capsule of eyes in an attempt to prevent PCO. However, for antimetabolite therapy to be effective, the agents must be present when the epithelial cell proliferation resumes. Sustained drug delivery systems have also been investigated as a means for preventing PCO. However, the effective time frame within which to apply these agents may be difficult to determine. PCO is believed to result primarily from the propagation of lens epithelial cells of the germinal layer. These cells eventually proliferate and migrate across the lens capsule into the optical zone. The timing of such an event is difficult to accurately target for treatment thereof.
Immunotoxins which are hybrid molecules composed of monoclonal antibodies chemically linked to toxic moieties, have also been used in the selective destruction of residual lens epithelial cells. The monoclonal antibody directs the toxic moiety to the target cell. The cell then internalizes the immunotoxin, thereby causing the vital biological processes of the cell to be compromised by the toxic moiety. Other efforts have been made to destroy residual lens epithelial cells. One such effort included the use of a fibroblastic growth factor bonded to a toxic moiety. However, monoclonal antibodies and fibroblastic growth factors are relatively expensive and difficult to produce on a reliable and consistent basis. Therefore, it is desirable to employ a method that provides selective destruction of residual lens epithelial cells without the costs and problems associated with monoclonal antibodies and growth factors.
Accordingly, a long felt need exists for a reliable and cost effective method of preventing posterior cellular opacification or secondary cataracts in cataract patients having IOL implants.